Complex neural representation of odour information in the olfactory bulb

The most important task of the olfactory system is to generate a precise representation of odour information under different brain and behavioural states. As the first processing stage in the olfactory system and a crucial hub, the olfactory bulb plays a key role in the neural representation of odours, encoding odour identity, intensity and timing. Although the neural circuits and coding strategies used by the olfactory bulb for odour representation were initially identified in anaesthetized animals, a large number of recent studies focused on neural representation of odorants in the olfactory bulb in awake behaving animals. In this review, we discuss these recent findings, covering (a) the neural circuits for odour representation both within the olfactory bulb and the functional connections between the olfactory bulb and the higher order processing centres; (b) how related factors such as sniffing affect and shape the representation; (c) how the representation changes under different states; and (d) recent progress on the processing of temporal aspects of odour presentation in awake, behaving rodents. We highlight discussion of the current views and emerging proposals on the neural representation of odorants in the olfactory bulb.     

Respiratory-phase-related coding of olfactory information in the olfactory bulb of awake freely-breathing rabbits

The "across-neuron pattern" theory of olfactory information coding states that odorants are represented by spatial patterns of activity produced across-neurons in the olfactory bulbs. The present study analyzes the different response patterns encoding olfactory information in both the inspiratory and expiratory phases of the respiratory cycles of awake freely-breathing rabbits. We recorded the single-unit responses of 31 neurons to 5 different odorants, 3 of which were repeatedly delivered 5 times each. These responses were characterized by the change in their mean firing activity during the inspiratory and expiratory phases of the respiratory cycles respectively. Their processing using principal component analyses revealed that both the inspiration- and the expiration-related across-neuron profiles of responses contained information appropriate to the specification of each odorant. It was therefore concluded that there was a dynamic representation of odorants in the olfactory bulb of awake freely-breathing animals. This alternate representation of odorants by two profiles and its physiological significance are discussed.     

Dense representation of natural odorants in the mouse olfactory bulb

In mammals, odorant molecules are thought to activate only a few glomeruli, leading to the hypothesis that odor representation in the olfactory bulb is sparse. However, the studies supporting this model used anesthetized animals or monomolecular odorants at limited concentration ranges. Using optical imaging and two-photon microscopy, we found that natural odorants at their native concentrations could elicit dense representations in the olfactory bulb. Both anesthesia and odorant concentration were found to modulate the representation density of natural odorants.     

Functional segregation of the inferior frontal gyrus for syntactic processes: a functional magnetic-resonance imaging study

We used functional magnetic resonance imaging in 18 normal volunteers to determine whether there is separate representation of syntactic, semantic, and verbal working memory processing in the left inferior frontal gyrus (GFi). We compared a sentence comprehension task with a short-term memory maintenance task to identify syntactic and semantic processing regions. To investigate the effects of syntactic and verbal working memory load while minimizing the differences in semantic processes, we used comprehension tasks with garden-path (GP) sentences, which require re-parsing, and non-garden-path (NGP) sentences. Compared with the short-term memory task, sentence comprehension activated the left GFi, including Brodmann areas (BAs) 44, 45, and 47, and the left superior temporal gyrus. In GP versus NGP sentences, there was greater activity in the left BAs 44, 45, and 46 extending to the left anterior insula, the pre-supplementary motor area, and the right cerebellum. In the left GFi, verbal working memory activity was located more dorsally (BA 44/45), semantic processing was located more ventrally (BA 47), and syntactic processing was located in between (BA 45). These findings indicate a close relationship between semantic and syntactic processes, and suggest that BA 45 might link verbal working memory and semantic processing via syntactic unification processes.     

The Effect of Individual Differences in Working Memory Capacity on Sentence Comprehension: An fMRI Study

This study explores the interaction between working memory systems and language processing by examining how differences in working memory capacity (WMC) modulates neural activation levels and functional connectivity during sentence comprehension. The results indicate that two working memory systems may be involved in sentence comprehension, the verbal working memory system and the episodic buffer, but during different phases of the task. A sub-region of the left inferior frontal gyrus (BA 45) was correlated with WMC during the probe and not during sentence reading while the only region to reveal a correlation with WMC during sentence reading was the posterior cingulate/precuneus area, a region linked to event representation. In addition, functional connectivity analysis suggests that there were two distinct networks affected by WMC. The first was a semantic network that included the middle temporal cortex, an anterior region of the inferior frontal gyrus and the inferior parietal region. The second included the posterior cingulate and BA 45 of the inferior frontal gyrus. We propose here that high capacity readers may generate an event representation of the sentence during reading that aids in comprehension and that this event representation involves the processing of the posterior cingulate cortex.     

Role of the executive function in the relationship between verbal working memory and long-term information

It is well known that long-term information contributes to verbal working memory. Although the phonological loop is assumed to have an important role in verbal working memory, the processing of long-term information is supposed to occur in another system, and the executive function is presumably involved in this process. Long-term information that affects verbal working memory can be divided into two types of representations: semantic information and long-term phonological knowledge. We used a dual-task method to investigate the role of the executive function in the processing of these two types of representation. We focused on the concreteness effect and the frequency effect, which are assumed to reflect semantic information and long-term phonological knowledge, respectively. The concreteness effect was banished when the executive function was disrupted by focusing on verbal semantic features. The frequency effect remained intact when the executive function was disrupted, while the burden on the phonological loop caused the effect to be decreased. We concluded that the executive function plays a crucial role in the processing of verbal semantic information, but not in the processing of long-term phonological knowledge.     

Odour suppression in binary mixtures

It has been suggested that odours causing stronger trigeminal activation suppress weaker trigeminal stimuli and that mixed olfactory-trigeminal stimuli suppress odorants that only activate one of these systems. Volunteer normosmic participants (n=20) were exposed to six odorants with varying trigeminal impact to test the hypothesis that more intense "trigeminal" odorants would suppress weaker trigeminal stimuli in binary odour mixtures. It was also hypothesised that stronger trigeminal odorants would dominate six-odour mixtures. The predicted linear pattern of suppression was not seen, with a quadratic model emerging from the data. Stronger trigeminal stimuli failed to dominate six-odour mixtures. Despite the fact that the major hypothesis was not supported, it can be hypothesised from this experiment that the effect of suppression in binary mixtures is reliant upon two major effects: (1) the association formed between odours and the multiple memory systems that they interact with during the encoding and recognition processes, and (2) the balance between activation of the olfactory and trigeminal systems.     

Trial-by-trial discrimination of three enantiomer pairs by neural ensembles in mammalian olfactory bulb

Populations of output neurons in the mammalian olfactory bulb (OB) exhibit distinct, widespread spatial and temporal activation patterns when stimulated with odorants. However, questions remain as to how ensembles of mitral/tufted (M/T) neurons in the mammalian OB represent odorant information. In this report, the single-trial encoding limits of random ensembles of putative single- and multiunit M/T cells in the anesthetized rat OB during presentations of enantiomers of limonene, carvone, and 2-butanol are investigated using simultaneous multielectrode recording techniques. The results of these experiments are: the individual constituents of our recorded ensembles broadly represent information about the presented odorants, the ensemble single-trial response of small spatially distributed populations of M/T neurons can readily discriminate between six different odorants, and the most consistent odorant discrimination is attained when the ensemble consists of all available units and their responses are integrated over an entire breathing cycle. These results suggest that small differences in spike counts among the ensemble members become significant when taken within the context of the entire ensemble. This may explain how ensembles of broadly tuned OB neurons contribute to olfactory perception and may explain how small numbers of individual units receiving input from distinct olfactory receptor neurons can be combined to form a robust representation of odorants.     

Executive functioning and olfactory identification in young adults with attention deficit-hyperactivity disorder

Young adults with attention deficit-hyperactivity disorder (ADHD; N = 105) were compared with a control group (N = 64) on 14 measures of executive function and olfactory identification using a 2 (group) X 2 (sex) design. The ADHD group performed significantly worse on 11 measures. No Group X Sex interaction was found on any measures. No differences were found in the ADHD group as a function of ADHD subtype or comorbid oppositional defiant disorder. Comorbid depression influenced the results of only 1 test (Digit Symbol). After IQ was controlled for, some group differences in verbal working memory, attention, and odor identification were no longer significant, whereas those in inhibition, interference control, nonverbal working memory, and other facets of attention remained so. Executive function deficits found in childhood ADHD exist in young adults with ADHD and are largely not influenced by comorbidity but may be partly a function of low intelligence.     

Effects of odor stimulation on antidromic spikes in olfactory sensory neurons

Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very large proportion of olfactory axons was activated by single strong odor stimuli.     

Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila

Aversive olfactory memory is formed in the mushroom bodies in Drosophila melanogaster. Memory retrieval requires mushroom body output, but the manner in which a memory trace in the mushroom body drives conditioned avoidance of a learned odor remains unknown. To identify neurons that are involved in olfactory memory retrieval, we performed an anatomical and functional screen of defined sets of mushroom body output neurons. We found that MB-V2 neurons were essential for retrieval of both short- and long-lasting memory, but not for memory formation or memory consolidation. MB-V2 neurons are cholinergic efferent neurons that project from the mushroom body vertical lobes to the middle superiormedial protocerebrum and the lateral horn. Notably, the odor response of MB-V2 neurons was modified after conditioning. As the lateral horn has been implicated in innate responses to repellent odorants, we propose that MB-V2 neurons recruit the olfactory pathway involved in innate odor avoidance during memory retrieval.     

成人数字、词语和视空间工作记忆广度的发展特征及影响因素

目的:考察成人(18~49岁)数字、词语和视空间工作记忆广度发展变化的趋势及其影响因素。方法:采用多维记忆评估量表中的3个工作记忆广度分测验对280名正常成人进行测查,并收集一般资料。结果:成人的数字、词语和视空间广度成绩随年龄的增长均呈下降趋势(F=2.96~6.87,P<0.01);出现随龄衰减现象的先后顺序依次为视空间广度、词语广度和数字广度;在记忆广度总成绩和大多数分测验成绩上男女无显著差异,仅在30-34岁年龄组,男性视空间广度位置的成绩好于女性(11.02±3.17/8.67±3.18,t=2.15,P<0.05)。逐步回归分析结果显示,教育是成人数字、词语和视空间广度的保护因素(Beta值=0.546,0.445,0.423;P<0.01)。结论:成人阶段数字、词语和视空间工作记忆广度的发展变化基本上趋于一致,并且受教育程度能对不同的工作记忆广度起促进作用。     

Responses of the rat olfactory epithelium to retronasal air flow

Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very nonpolar, hydrophobic odorants were used. Although the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the nonpolar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recordings from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally versus retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes.     

Iron-induced oxidative stress modulates olfactory learning and memory in honeybees

Reactive oxygen species (ROS)-mediated oxidative stress tends to increase with environmental stress, aging, and age-related diseases resulting in progressive neuronal dysfunction. The purpose of the present study was to examine whether or not oxidative stress can be induced into the antennal lobes of the honeybee brain by injecting ferrous ammonium citrate (FAC). Proboscis Extension Reflex conditioning procedure was used to assay subjects' responses to odorants for evaluating the effect of oxidative stress on the olfactory learning and memory. FAC-induced inhibitory effect on olfactory learning and memory was dose-and time-dependent. Injections of reduced glutathione (GSH) into the antennal lobes before FAC treatment blocked oxidative stress-mediated inhibitory effect. Injections of VK-28 prior to FAC treatment overcame oxidative stress-mediated inhibitory response. However, injections of GSH into the antennal lobes prior to mianserin/dsRNA treatment did not reverse octopamine receptor disruption-mediated inhibitory response. These results indicate that normal cellular redox is crucial for olfactory processing, and chelation of iron prevents ROS-mediated oxidative stress. Furthermore, octopamine receptor disruption, and FAC-mediated oxidative stress confer two independent mechanisms that impair olfactory learning and memory in honeybees.     

Odor representation and discrimination in mitral/tufted cells of the rat olfactory bulb

Extracellular single-unit responses to odorants with various properties were recorded from mitral/tufted cells over large areas of the olfactory bulb of anesthetized rats. Each cell was exposed to one stimulus set consisting of five different odorants each at five concentrations. The resulting concentration-response profiles were compared. All mitral/tufted cells examined responded to two or more odorants, and the largest proportion of the cells were sensitive to all five odorants. Cells unresponsive to all five odorants regardless of concentration were not observed. Mitral/tufted cells sensitive to all three of the odorants that are known to evoke maximal electro-olfactograms in different regions of the olfactory epithelium were distributed widely throughout the olfactory bulb. There were no significant differences in latencies of odor responses either across recording sites or across odorants. A comparison of the concentration-response profiles suggested that all of the mitral/tufted cells were equally capable of responding to any odorant with their own distinctive pattern, but that the cells tended to show an identical pattern rather than variable pattern of response to different odorants. Five mitral/tufted cells isolated within 800 m of one electrode track showed different concentration-response profiles. Of 18 simultaneously recorded spike pairs with different amplitudes and discharge patterns recorded incidentally through one electrode at different sites, 10 had different and 8 had identical response patterns to odorants. These results suggest that: (1) mitral/tufted cells are sensitive to a broad spectrum of odorants, but respond with their own patterns to odorants; (2) odor discrimination is not uniform in neighboring cells, and a discrimination unit is comprised of a single cell.     

Stimulation of the olfactory epithelium with odorants in gaseous and aqueous phases.

The olfactory epithelia of the bullfrog and the carp were stimulated with various odorants in the gaseous and/or aqueous phases. Some ionic solutions were also applied. 1. By recording the induced waves in the olfactory bulb, it was shown that the bullfrog responds to odorants in the two phases, but the carp can respond only to odorants in the aqueous phase. 2. Comparison of the stimulative effects of the same odorants in the two phases were made in the bullfrog. Although various response patterns to gaseous and aqueous stimuli of single cells in the olfactory bulb were found in most cases, a difference in the application methods of vapors and solutions made such comparison difficult. 3. The same single cells in the olfactory bulb usually responded to various odorous vapors and solutions as well as to ions in different patterns. When the responses to the vapors and solutions of the same odorants of different concentrations were compared, different patterns were also found.     

Selective loss of cholinergic neurons projecting to the olfactory system increases perceptual generalization between similar, but not dissimilar, odorants

The neuromodulator acetylcholine is thought to modulate information processing in the olfactory system. The authors used 192 IgG-saporin, a lesioning agent selective for basal forebrain cholinergic neurons, to determine whether selective lesions of cholinergic neurons projecting to the olfactory bulb and cortex affect odor perception in rats. Lesioned and sham-operated rats were tested in an olfactory generalization paradigm with sets of chemically related odorants (n-aliphatic aldehydes, acids, and alcohols). Lesioned rats generalized more between chemically similar odorants but did not differ from controls in their response to chemically unrelated odorants or in acquisition of the conditioned odor. Results show that cholinergic inputs to the olfactory system influence perceptual qualities of odorants and confirm predictions made by computational models of this system.     

Specific Memory Impairment Following Neonatal Encephalopathy in Term-Born Children

This study examines short-term memory, verbal working memory, episodic long-term memory, and intelligence in 32 children with mild neonatal encephalopathy (NE), 39 children with moderate NE, 10 children with NE who developed cerebral palsy (CP), and 53 comparison children, at the age of 9 to 10 years. Results: in addition to a global effect on intelligence, NE had a specific effect on verbal working memory, verbal and visuo-spatial long-term memory, and learning, which was associated with degree of NE. Although these memory problems occurred in children without CP, they were more pronounced when children had also developed CP.     

Specific memory impairment following neonatal encephalopathy in term-born children

This study examines short-term memory, verbal working memory, episodic long-term memory, and intelligence in 32 children with mild neonatal encephalopathy (NE), 39 children with moderate NE, 10 children with NE who developed cerebral palsy (CP), and 53 comparison children, at the age of 9 to 10 years. Results: in addition to a global effect on intelligence, NE had a specific effect on verbal working memory, verbal and visuo-spatial long-term memory, and learning, which was associated with degree of NE. Although these memory problems occurred in children without CP, they were more pronounced when children had also developed CP.